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Physical examination of knee ligament injuries often is considered subjective and imprecise as the result of various factors affecting its reliability. Magnetic resonance imaging is widely used but lacks information on ligament function and is costly. Stress radiography is commonly employed, but alternatives are sought because of radiation exposure and the need for a physician's presence during the procedure. Ultrasonography represents a noninvasive, rapid, and cost-effective method for assessing knee injuries. This Technical Note presents stress ultrasonography protocols for evaluating medial and lateral tibiofemoral openings in patients with posteromedial corner and/or posterolateral corner injuries. The ultrasonography examination parameters are detailed for both the medial collateral ligament and lateral collateral ligament evaluation. Studies have associated certain degrees of tibiofemoral opening with knee ligament injuries, aiding surgeons in surgical decision-making. Examination with stress ultrasonography offers a dynamic and reproducible method without adverse effects for patients, potentially expediting the diagnosis and treatment of multiligament knee injuries.
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OBJECTIVE: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS. METHODS: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models. RESULTS: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups. CONCLUSIONS: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y12(P2Y12) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age.
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Síndrome Coronariana Aguda , Aspirina , Fibrilação Atrial , Fibrinolíticos , Hemorragia , Intervenção Coronária Percutânea , Pirazóis , Piridonas , Humanos , Idoso , Piridonas/uso terapêutico , Piridonas/efeitos adversos , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Masculino , Feminino , Aspirina/uso terapêutico , Aspirina/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Fatores Etários , Hemorragia/induzido quimicamente , Pessoa de Meia-Idade , Fibrinolíticos/uso terapêutico , Fibrinolíticos/efeitos adversos , Vitamina K/antagonistas & inibidores , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: To derive and validate internally a novel risk assessment tool to identify young children at risk for all-cause mortality ≤60 days of discharge from hospitals in sub-Saharan Africa. STUDY DESIGN: We performed a prospective observational cohort study of children aged 1-59 months discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania and John F. Kennedy Medical Center in Monrovia, Liberia (2019-2022). Caregivers received telephone calls up to 60 days after discharge to ascertain participant vital status. We collected socioeconomic, demographic, clinical, and anthropometric data during hospitalization. Candidate variables with P < .20 in bivariate analyses were included in a multivariable logistic regression model with best subset selection to identify risk factors for the outcome. We internally validated our tool using bootstrapping with 500 repetitions. RESULTS: There were 1933 young children enrolled in the study. The median (IQR) age was 11 (4, 23) months and 58.7% were males. In total, 67 (3.5%) died during follow-up. Ten variables contributed to our tool (total possible score 82). Cancer (aOR 10.6, 95% CI 2.58, 34.6), pedal edema (aOR 6.94, 95% CI 1.69, 22.6), and leaving against medical advice (aOR 6.46, 95% CI 2.46, 15.3) were most predictive of post-discharge mortality. Our risk assessment tool demonstrated good discriminatory value (optimism corrected area under the receiver operating characteristic curve 0.77), high precision, and sufficient calibration. CONCLUSIONS: After validation, this tool may be used to identify young children at risk for post-discharge mortality to direct resources for follow-up of high-risk children.
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Alta do Paciente , Humanos , Tanzânia/epidemiologia , Lactente , Masculino , Feminino , Medição de Risco/métodos , Pré-Escolar , Estudos Prospectivos , Libéria/epidemiologia , Alta do Paciente/estatística & dados numéricos , Fatores de Risco , Mortalidade da CriançaRESUMO
Background: Biomechanical assessment of meniscal repairs is essential for evaluating different meniscal suturing methods and techniques. The continuous meniscal suture technique is a newer method of meniscal repair that may have biomechanical differences compared with traditional techniques. Purpose: To evaluate the displacement, stiffness after cyclical loading, and load to failure for a continuous vertical inside-out meniscal suture versus a traditional vertical inside-out meniscal suture in a porcine medial meniscus. Study Design: Controlled laboratory study. Methods: A total of 28 porcine knees were acquired and divided into 2 test groups of 14 medial meniscus each. A 2.0-cm longitudinal red-white zone cut was made in the body of the medial meniscus for each knee. The continuous suture (CS) group received 4 vertical stitches performed with a continuous vertical meniscal suture technique, and the inside-out suture (IO) group received a traditional vertical suture with 4 stitches. Two traction tapes were passed between the sutures and positioned in the biomechanical testing fixture device. Each specimen underwent load-to-failure testing at 5 mm/s, and displacement, system stiffness, and maximum load to failure were compared between the groups. Results: The displacement after the cyclic test was 0.53 ± 0.12 and 0.48 ± 0.07 mm for the CS and IO groups, respectively. There was no significant difference between the groups (P = .2792). The stiffness at the ultimate load testing was 36.3 ± 1.9 and 35.3 ± 2.4 N/mm for groups CS and IO, respectively, with no significant difference between the groups (P = .2557). In the load-to-failure test, the ultimate load was 218.2 ± 63.9 and 238.3 ± 71.3 N in the CS and IO groups, respectively, with no significant group differences (P = .3062). Conclusion: A continuous vertical meniscal suture created a configuration for treating longitudinal meniscal lesions that was beneficial and biomechanically similar to a traditional vertical suture technique. Clinical Relevance: The study findings indicate that use of the continuous vertical inside-out meniscal suture technique is a possible therapeutic option.
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Dor Abdominal , Dor Crônica , Feminino , Humanos , Adulto Jovem , Adulto , Dor Abdominal/etiologiaRESUMO
Allogeneic hematopoietic stem cell transplantation (alloSCT) is, in many clinical settings, the only curative treatment for acute myeloid leukemia (AML). The clinical benefit of alloSCT greatly relies on the graft-versus-leukemia (GVL) effect. However, AML relapse remains the top cause of posttransplant death; this highlights the urgent need to enhance GVL. Studies of human GVL have been hindered by the lack of optimal clinically relevant models. In this article, we report, the successful establishment of a novel (to our knowledge) humanized GVL model system by transplanting clinically paired donor PBMCs and patient AML into MHC class I/II knockout NSG mice. We observed significantly reduced leukemia growth in humanized mice compared with mice that received AML alone, demonstrating a functional GVL effect. Using this model system, we studied human GVL responses against human AML cells in vivo and discovered that AML induced T cell depletion, likely because of increased T cell apoptosis. In addition, AML caused T cell exhaustion manifested by upregulation of inhibitory receptors, increased expression of exhaustion-related transcription factors, and decreased T cell function. Importantly, combined blockade of human T cell-inhibitory pathways effectively reduced leukemia burden and reinvigorated CD8 T cell function in this model system. These data, generated in a highly clinically relevant humanized GVL model, not only demonstrate AML-induced inhibition of alloreactive T cells but also identify promising therapeutic strategies targeting T cell depletion and exhaustion for overcoming GVL failure and treating AML relapse after alloSCT.
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Austropuccinia psidii is a biotrophic fungus that causes myrtle rust. First described in Brazil, it has since spread to become a globally important pathogen that infects more than 480 myrtaceous species. One of the most important commercial crops affected by A. psidii is eucalypt, a widely grown forestry tree. The A. psidii-Eucalyptus spp. interaction is poorly understood, but pathogenesis is likely driven by pathogen-secreted effector molecules. Here, we identified and characterized a total of 255 virulence effector candidates using a genome assembly of A. psidii strain MF-1, which was recovered from Eucalyptus grandis in Brazil. We show that the expression of seven effector candidate genes is modulated by cell wax from leaves sourced from resistant and susceptible hosts. Two effector candidates with different subcellular localization predictions, and with specific gene expression profiles, were transiently expressed with GFP-fusions in Nicotiana benthamiana leaves. Interestingly, we observed the accumulation of an effector candidate, Ap28303, which was upregulated under cell wax from rust susceptible E. grandis and described as a peptidase inhibitor I9 domain-containing protein in the nucleus. This was in accordance with in silico analyses. Few studies have characterized nuclear effectors. Our findings open new perspectives on the study of A. psidii-Eucalyptus interactions by providing a potential entry point to understand how the pathogen manipulates its hosts in modulating physiology, structure, or function with effector proteins.
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The intra-articular injury most often associated with a chronic anterior cruciate ligament tear involves the posterior horn of the medial meniscus. A specific type of medial meniscal injury, called a ramp lesion, has received greater attention for identification and treatment because of its considerable incidence and diagnostic difficulty. Based on their location, these lesions may be arthroscopically "hidden" during traditional anterior visualization. The purpose of the present Technical Note is to describe the Recife maneuver. This maneuver diagnoses injuries to the posterior horn of the medial meniscus using additional arthroscopic management through a standard portal. The Recife maneuver is performed with the patient in the supine position. A 30° arthroscope is inserted through the anterolateral portal, and the posteromedial compartment is accessed according to the transnotch view (modified Gillquist view). In the proposed maneuver, with the knee in 30° of flexion, a valgus stress with internal rotation is performed, followed by palpation of the popliteal region and digital pressure on the joint interline. This maneuver allows a greater visualization of the posterior compartment, allowing the diagnostic evaluation of the integrity between the meniscus and the capsule, in a safer way, being able to identify ramp tears without the need to create a posteromedial portal. We recommend that the addition of the diagnostic visualization step of the posteromedial compartment as described by the Recife maneuver be performed to assess the meniscal status in routine anterior cruciate ligament reconstruction.
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The indications for combining anterior cruciate ligament reconstruction with anterolateral ligament reconstruction have increased considerably in recent years since several anatomical, clinical, and biomechanical studies have proven the importance of the anterolateral periphery in knee rotational stability. Much is still being discussed on how to combine these techniques in terms of which grafts and fixation options to use, as well as avoiding tunnel convergence. This study aims to describe anterior cruciate ligament reconstruction with a triple-bundle semitendinosus tendon graft all-inside technique combined with an anterolateral ligament reconstruction maintaining the gracilis tendon insertion on the tibia, using independent anatomical tunnels. With this, we were able to reconstruct both using only hamstring autografts, reducing morbidity in other possible donor areas, in addition to allowing stable fixation of both grafts without tunnel convergence.
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BACKGROUND: To measure the impact of the COVID-19 pandemic on the management of patients with carotid artery stenosis. METHODS: We prospectively collected data from 25 centers (19 centers in the United States and 6 centers internationally) on postponed carotid artery operations between March 2020 and January 2022. We describe the characteristics of these patients and their planned operations, along with outcomes including mortality and neurological deterioration during the period of operative delay due to the COVID-19 pandemic. RESULTS: A total of 1,220 vascular operations were postponed during the pandemic, of them 96 patients presented with significant carotid stenosis (median stenosis of 71%; interquartile range; 70-80) and 80% of them were planned for carotid endarterectomy. Most patients were asymptomatic (69%), and 31% of patients were symptomatic (16% of patients had a stroke, 15% of patients had a transient ischemic attack, and 1% of patients experienced amaurosis fugax). The median length of surgical delay was 71 days (interquartile range: 45.5, 115.5). At the data entry time, 62% of patients had their carotid operations postponed and successfully completed. Most postponements (72%) were due to institutional policies aimed at resource conservation. During the delay, no patient decompensated or required an urgent operation. A total of 5 patients (5%) with carotid stenosis died while awaiting operations due to COVID-19. CONCLUSIONS: Our study of a cohort of patients with carotid artery stenosis who underwent a median delay of 71 days during the COVID-19 pandemic showed a disparate operation delay between US regions and internationally, most postponements were due to hospital policy, and none of the patients deteriorated or required an emergency surgery during the delay.
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COVID-19 , Estenose das Carótidas , Endarterectomia das Carótidas , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/epidemiologia , Pandemias , Resultado do Tratamento , Endarterectomia das Carótidas/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Artérias CarótidasRESUMO
Available treatments for leishmaniasis have been widely used since the 1940s but come at a high cost, variable efficacy, high toxicity, and adverse side-effects. 3,3',5,5'-Tetramethoxy-biphenyl-4,4'-diol (TMBP) was synthesized through laccase-catalysis of 2,6-dimethoxyphenol and displayed antioxidant and anticancer activity, and is considered a potential drug candidate. Thus, this study aimed to evaluate the anti-leishmanial effect of TMBP against promastigote and amastigote forms of Leishmania (L.) amazonensis and investigated the mechanisms involved in parasite death. TMBP treatment inhibited the proliferation (IC50 0.62-0.86 µM) and induced the death of promastigote forms by generating reactive oxygen species and mitochondrial dysfunction. In intracellular amastigotes, TMBP reduced the percentage of infected macrophages, being 62.7 times more selective to the parasite (CC50 53.93 µM). TMBP did not hemolyze sheep erythrocytes; indicative of low cytotoxicity. Additionally, molecular docking analysis on two enzyme targets of L. amazonensis: trypanothione reductase (TR) and leishmanolysin (Gp63), suggested that the hydroxyl group could be a pharmacophoric group due to its binding affinity by hydrogen bonds with residues at the active site of both enzymes. TMBP was more selective to the Gp63 target than TR. This is the first report that TMBP is a promising compound to act as an anti-leishmanial agent.
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Antiprotozoários , Leishmania mexicana , Leishmania , Animais , Ovinos , Camundongos , Simulação de Acoplamento Molecular , Antiprotozoários/farmacologia , Antiprotozoários/química , Camundongos Endogâmicos BALB CRESUMO
CASE: A 62-year-old male patient suffered an irreducible posterolateral knee dislocation after a horse fell on him. The left knee was slightly flexed with a medial dimple sign present. The medial retinaculum, medial patellofemoral ligament, posteromedial corner structures, and vastus medialis obliquus (VMO) muscle were incarcerated in the medial joint. An open reduction and the medial retinaculum and VMO gap were repaired, and the knee was stabilized in an external fixator for 4 weeks. At 32-month follow-up, the patient had almost full knee motion and good subjective outcomes with moderate residual joint laxity. CONCLUSION: Early clinical diagnosis of irreducible knee dislocations and emergent open reduction should be performed to reduce the risk of soft-tissue compromise.
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Luxações Articulares , Luxação do Joelho , Masculino , Humanos , Animais , Cavalos , Articulação do Joelho , Luxação do Joelho/diagnóstico por imagem , Luxação do Joelho/cirurgia , Luxações Articulares/cirurgia , Ligamentos Articulares , Músculo QuadrícepsRESUMO
Free-floating bike-sharing systems can have a positive influence on the mobility of urban centers and developing efficient localization strategies is crucial to avoid crowding at peak times and increase service availability. Our study aims to efficiently resolve the location of virtual bike stations in a Latin American city through a geospatial data wrangling methodology that allows us to respond opportunely to the potential demand forecasted for the city. This approach is implemented in Python, and it uses the Geopandas and LocalSolver libraries to determine locations for the virtual bike stations that maximize the system coverage. The decision-making process is supported by a binary integer mathematical programming model, and the instances are built from intercity travel surveys that provide realistic data based on travel demand. The developed decision support system prototype provides a recommendation about where virtual bike stations should be located during peak hours and improve general availability by more than 37%. Moreover, when the system's users participate in the relocation of bicycles, the model can eliminate up to 80% of the CO2 emissions and nearly 50% of the operational costs associated with the relocation process.
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Objectives: Our purpose was to evaluate the clinical results of PCL tibial avulsion fracture fixation performed with 4 mm cancellous screws using a dual posteromedial (PM) portal technique. Methods: In a prospective study, we followed 12 patients submitted to PCL tibial insertion avulsion arthroscopic fixation using dual PM portals with cancellous screws from March 2014 to Jan 2020. The proximal higher PM portal served as an instrument portal and provided an optimal trajectory for arthroscopic screw fixation of larger PCL avulsion fractures. The lower PM portal was used as a viewing portal. Results: Significant improvements were found between the preoperative and postoperative mean Lysholm scores at six months. The preoperative IKDC score mean of 10.13 increased to 89.3 at the end of six months. Minor adverse results with this technique were: grade I on posterior sag in five knees (41.6%), temporary stiffness in two cases (16.7 %), delayed union in one patient (8.3 %), and difficulty squatting at the end of six months in one patient (8.3%). Temporary extension lag was present in two individuals (16.7%), and fixed subtle flexion deficit of 3-5 degrees occurred in one individual (8.3 %). Conclusion: The outcomes obtained with the proposed technique were similar to those obtained with open techniques, although mild flexion deficits and discreet posterior sag may be present in a significant number of cases. Level of Evidence II; Prospective Cohort Study .
Objetivos: O objetivo foi avaliar os resultados clínicos da fixação da fratura da avulsão tibial PCL realizada com parafusos esponjosos de 4 mm, utilizando uma técnica de portal postero-medial (PM) duplo. Métodos: Em um estudo prospectivo, acompanhamos 12 pacientes submetidos à fixação da avulsão tibial de inserção PCL por via artroscópica utilizando portais duplos PM com parafusos esponjosos de março de 2014 a janeiro de 2020. O portal PM proximal superior serviu como um portal de instrumentos e forneceu uma trajetória ideal para a fixação artroscópica com parafusos de fixação de fraturas avulsas PCL maiores. O portal PM inferior foi usado como um portal de visualização. Resultados: Foram encontradas melhorias significativas entre o pré-operatório e o pós-operatório, com pontuação média de Lysholm aos seis meses. A pontuação média do IKDC pré-operatório de 10,13 aumentou para 89,3 no final dos seis meses. Os resultados adversos menores com esta técnica foram: grau I na flacidez posterior de cinco joelhos (41,6%), rigidez temporária em dois casos (16,7%), união tardia em um paciente (8,3%) e dificuldade de agachamento ao final de seis meses em um paciente (8,3%). O atraso temporário da extensão estava presente em dois indivíduos (16,7%) e o déficit de flexão sutil fixo de 3-5 graus ocorreu em um indivíduo (8,3%). Conclusão: Os resultados obtidos com a técnica proposta foram similares aos obtidos com técnicas abertas, embora déficits leves de flexão e discreta flacidez posterior possam estar presentes em um número significativo de casos. Nível de Evidência II; Estudo de Coorte Prospectivo.
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Vascular research questions can be answered using various study designs. Observational studies are used frequently to address a wide range of clinical questions when randomized clinical trials are not feasible or practical. One of the powerful vascular research tools is the cohort study. The cohort study is a reliable observational study design in which individuals who share a common characteristic (a cohort) are followed over time and their outcomes are assessed at various intervals. This review focuses on the essential characteristics, design, implementation, bias, validity, and clinical significance of cohort studies and provides illustrative examples. A cohort study can be either a prospective or a retrospective study, depending on whether the outcome occurred before or after the enrollment of the cohort. Each type has its advantages and disadvantages. Confounding, selection, and information biases can all occur in cohort studies. Applications of the cohort study design include studying the natural history of a disease, describing a condition's frequency, and investigating multiple outcomes simultaneously.
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Projetos de Pesquisa , Procedimentos Cirúrgicos Vasculares , Humanos , Estudos de Coortes , Estudos Retrospectivos , Estudos Prospectivos , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Estudos Observacionais como AssuntoRESUMO
The present study proposes the production of vinegars from pineapple processing residues as an eco-friendly strategy for adding value and economic strengthening of the production chain. Pineapple pulp and peel wines were produced and acetificated to vinegar by wild strains of acetic bacteria using Orlean's method (traditional system) followed by enrichment with leaf extract of Red-Jambo, Syzygium malaccense. Appreciable phenolic contents and antioxidant potential were found in pulp and peel vinegars with the added leaf extract. Catechin, epicatechin and caffeic, p-coumaric, ferulic, and gallic acids were the main phenolic compounds found in peel vinegar. The enrichment of the vinegar with the extract promoted an increase in the content of polyphenols (443.6-337.3 mg GAE/L) and antioxidant activity. Peel wines presented higher luminosity (L*) and higher saturation index (C*), and their color tended more toward yellow than pulp wines. Acetification reduced the saturation index (C*) and led to the intensification of the hue angle in the peels vinegar. Each type of pineapple vinegar produced showed biocidal activity against different bacteria and yeast, and the addition of leaf extract potentiated the antimicrobial activity of peel vinegar, especially against Staphalococcus aureus. The vinegars developed could find an attractive market niche in the food sector.
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Ananas , Syzygium , Vinho , Ácido Acético/química , Ananas/química , Vinho/análise , Fenóis/química , Antioxidantes/química , Saccharomyces cerevisiae , Extratos VegetaisRESUMO
Obesity is associated with other diseases such as diabetes and cancer. Botryosphaeran, a fungal (1â3)(1â6)-ß-d-glucan, is described to present antimutagenic, hypoglycemic, hypocholesterolemic, and antitumor activities when administered by gavage over 15 days in rats and mice. Thus, the present study aims to analyze the metabolic effects of Botryosphaeran (12 mg/kg body weight/day) treatment over 30 days in obese Wistar male rats. Obesity was induced in the rats by a high-fat/high-sugar diet for 8 weeks. Control rats received a standard diet. On the 5th week, Botryosphaeran treatment commenced. Groups: control, obese, and obese+Botryosphaeran 30 days. In the 8th week, obesity was characterized. Feed intake, glucose and lipid profiles, glucose tolerance, and insulin sensitivity were analyzed. Obese rats showed accumulation of visceral adipose tissue, reduction of muscle mass, glucose intolerance, insulin resistance, hyperglycemia, and dyslipidemia. Botryosphaeran effectively reduced weight gains and the accumulation of retroperitoneal adipose tissue, corrected the levels of glucose, triglycerides, and very low-density lipoprotein-cholestrol, and improved insulin sensitivity. Treatment for 30 days was effective in maintaining the beneficial effects demonstrated by this ß-glucan when administered for 15 days without promoting side effects. Treatment with (1â3)(1â6)-ß- d-glucan presented anti-obesogenic and beneficial metabolic effects in Wistar rats; important for the treatment of obesity and its comorbidities.
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Resistência à Insulina , beta-Glucanas , Animais , Glicemia , Dieta Hiperlipídica , Glucanos/farmacologia , Glucose , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina , Lipoproteínas LDL , Masculino , Camundongos , Obesidade/metabolismo , Ratos , Ratos Wistar , Açúcares , Triglicerídeos/metabolismo , beta-Glucanas/farmacologiaRESUMO
Several biological activities of the fungal exopolysaccharide (1 â 3)(1 â 6)-ß-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal ß-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal ß-glucan a new possibility for complementary treating acute and chronic inflammation.
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Hiperalgesia , beta-Glucanas , Administração Oral , Produtos da Oxidação Avançada de Proteínas/metabolismo , Animais , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Glucanos/efeitos adversos , Glucanos/farmacologia , Glucanos/uso terapêutico , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-10 , Leucócitos/patologia , Camundongos , Nociceptividade , beta-Glucanas/efeitos adversos , beta-Glucanas/farmacologia , beta-Glucanas/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.
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Breast cancer is the most common cancer worldwide among the female population. The fungal exopolysaccharide botryosphaeran is a (1â3)(1â6)-ß-D-glucan with limited solubility in water that can be promoted through carboxymethylation. Thus, the aim of this study was to examine in-vitro anticancer effects of carboxymethylated-botryosphaeran (CM-BOT) on breast cancer MCF-7 cells cultivated in multicellular tumor spheroids (MCTS). CM-BOT (≥ 600 µ/ml) decreased the viability (resazurin assay) of MCF-7 grown in monolayers after 24 hr incubation. Although CM-BOT did not markedly alter viability of MCTS in the resazurin assay after 24, 48 or 72 hr, CM-BOT ≥ 600 µg/ml produced cell-death by apoptosis after 72 hr utilizing the triple staining assay and labeling dead cells with propidium iodide, which can also be visualized on the architecture of MCTS. CM-BOT (1000 µg/ml) inhibited cell proliferation, which resulted in MCTSs with smaller diameters than controls. CM-BOT at all concentrations examined decreased the ability of MCF-7 to form colonies and to migrate in the extracellular matrix. This is the first report using MCTS-architecture to study anti-tumor effects of ß-glucans. Our findings are important in the search for compounds for use in breast cancer therapy, or as adjuvants in reducing the adverse effects of mammary tumor chemotherapy.